Poliovirus infection can cause a debilitating paralytic disease and, in rare cases, death. The first reports of poliomyelitis can be traced back to the early nineteenth century in Europe and the US. During the next 100 years or so, polio epidemics became more frequent and, along with them, an increase in the age and disease severity of those infected. By 1952, cases of paralytic polio peaked at over 21,000 in the US. It is no wonder that 50 years ago this year, Jonas Salk was hailed a hero with the announcement that he had developed a safe and effective vaccine. The stage had been set for the eradication of polio, but in 2005, how near are we to this ideal?

The Salk vaccine (IPV) is prepared from inactivated polioviruses of the three known serotypes (types 1, 2 and 3) and is administered by subcutaneous injection. It induces circulating neutralizing antibodies but not intestinal immunity. The vaccine therefore protects against polio paralysis but does not prevent poliovirus transmission via the fecal-oral route, the primary route of infection. After the Salk vaccine was licensed, Albert Sabin developed a live oral vaccine (OPV), which consists of the three attenuated viral strains. Unlike IPV, the live vaccine replicates in the gut, where it induces neutralizing antibodies, and was rapidly adopted for several reasons. Because OPV is an oral vaccine, sterile injection equipment and trained health workers are not required for its administration. The vaccine is also relatively cheap to produce (at present, US$0.05–0.08 per dose) but, perhaps more importantly, the vaccine induces mucosal immunity against wild-type virus and can result in passive immunization of unvaccinated people because of shedding of the vaccine virus in fecal matter.

In 1988, the World Health Assembly announced a program for the eradication of poliomyelitis by 2000. Because of the advantages offered by OPV, it was selected for this mammoth task. Despite missing its original target year of 2000, the polio eradication initiative has made some successful inroads. In September 1994, the Western Hemisphere was certified free of indigenous wild poliovirus. Statistics from Rotary International, a key funding body of the eradication initiative, showed that in 1988, 10% of the world's children lived in polio-free countries, compared with 70% by July 2004. With such impressive statistics, it is easy to imagine that poliovirus could be the next pathogen after smallpox to be eliminated. However, the eradication initiative has recently been dealt several blows.

In rare cases (about one in every 750,000 people), vaccination with OPV can induce vaccine-associated paralytic disease. Indeed, this is why the US has used IPV since 2000. Nevertheless, the advantages of using OPV in developing nations seemed to outweigh this small risk. But in the summer of 2000, there was an outbreak of polio in Hispaniola, an island that had been disease free for many years. The outbreak was not due to importation, as expected, but was due to a mutant form of the type I Sabin strain that could spread from person to person. Low natural immunity to wild poliovirus and low vaccine coverage in the area probably provided the selection pressure for the evolution of this mutant strain. Subsequently, other cases of virus revertants were documented in the Philippines and Madagascar. This raises the thorny issue of what happens if and when poliovirus is 'eradicated'. It seems that continued vaccination with OPV would be required to prevent mutant viruses from arising. But persuading poorer countries to continue costly vaccination campaigns will be difficult. Alternatively, the Salk vaccine could replace OPV before final cessation of polio immunization, but this would be even more costly, at least in the short term.

Another blow to the eradication campaign came in 2002, when Muslim clerics in northern Nigeria led a boycott against immunizations, claiming the vaccine was contaminated with human immunodeficiency virus and infertility agents by Western powers to depopulate the Muslim world. Although vaccination resumed after intense international pressure and the identification of an Islamic nation as a supplier for OPV, by then the number of polio cases in Nigeria represented more than half of all new cases worldwide by February 2004. Moreover, the boycott is blamed for the import of polio cases in eight other previously polio-free African nations. Clearly the political climate of the twenty-first century adds a new twist to the eradication program.

A related political issue is bioterrorism. Because poliovirus can be synthesized from published sequences of the wild-type virus strains, the potential still exists for its reintroduction by 'rogue scientists' after eradication. Unnecessary lab stocks must be destroyed and high-security containment facilities must house the remaining stocks to avoid inadvertent release of laboratory viruses. Although this was achieved previously with smallpox virus, it must be remembered wild poliovirus resides in fecal matter and therefore it is highly likely that many routine stool specimens in diagnostic laboratories could contain the virus. Eliminating this source of poliovirus may prove much more difficult.

In the 50 years since the advent of the Salk vaccine, where do we stand in our fight against polio? Clearly, we have made great strides in our attempt to make poliovirus follow the fate of the smallpox virus. Indeed, no new cases of type 2 wild poliovirus have been reported since 1999. Nevertheless, in 2005 we are faced with several challenges. Perhaps the greatest is what the endgame vaccine strategy after global certification of poliovirus eradication should be. Many possibilities exist, such as the continued use of OPV or replacement with IPV. This may have to be decided on a region-by-region basis. It is therefore critical that public health experts and healthcare policymakers debate the right path as we approach, one hopes, the last chapter in the history of poliomyelitis.